Texas A&M University and University of Texas at Austin researchers have discovered that in dogs with naturally occurring spinal cord injury, a drug that blocks matrix metalloproteinases (MMPs) allows the bladder to stretch more easily as it fills. Such a change will likely reduce the discomfort that is commonly associated with the inability to void urine after spinal cord injury and may improve bladder function.
This clinical trial, evaluated 93 dogs that sustained naturally occurring spinal cord injuries resulting from disc herniation. These injuries are most common in dachshunds, a breed that has a 20 percent lifetime risk of developing disc herniation, which can often cause sudden spinal cord injuries, according to Dr. Jonathan Levine, a professor of neurology and neurosurgery and department head of Small Animal Clinical Sciences in Texas A&M’s College of Veterinary Medicine & Biomedical Sciences (CVM).
“This breed has degeneration of their discs, including changes like dehydration and mineralization, starting early in life,” Levine said. “Because they have this early onset degeneration, dachshunds are set up to have disc herniation at a higher rate than other breeds.
“For a dachshund, these disc herniations consist of rapid displacement of the disc and bruising plus compression of the spinal cord,” he said.
This clinical trial, funded by the U.S. Department of Defense and published in the 2017 May issue of the Journal of Neurotrauma, was based upon earlier studies led by Linda Noble-Hauesslein at the University of Texas at Austin, in collaboration with colleagues at the University of California at San Francisco. Those early study were the first to demonstrate that MMPs, present in the injured spinal cord, contributed to the long-term loss of function after spinal cord injury. These encouraging findings led to the two-cohort clinical trial in spinal cord injured dogs in which Levine and his team administered the MMP inhibitor GM6001 to one set of dogs and provided a placebo to another set.
It is often difficult to empty the bladder after spinal cord injury and this can result in an increase in pressure within the organ. Using a technique called cystometry, the researchers measured the pressure in the bladder and found that dogs treated with GM6001 showed a greater capacity to stretch in response to filling (called compliance).
“We were trying to figure out how they recover from a urinary standpoint. Nobody knew. We knew a little bit just observing the dogs, whether they urinated again or not after their injuries,” Levine said. “What we found was that dogs that got the drug had bladders that were a little more forgiving, or a little more stretchy, compared to dogs that didn’t.”
The results, according to Levine, have significant implications for humans with spinal cord injuries as well.
“These injuries are actually very similar to traumatic spinal cord injuries in people, where there is compression and bruising of the cord,” he said. “People with injuries often have bladders that don’t stretch very well, so they might fill just a small amount of urine and then they have to empty. They have bladder urgency; it’s very uncomfortable.
“If you talk to people with spinal cord injury or you look at the literature, what you learn is that recovery of urinary function is as important or more important to those individuals than walking,” he said.
As many as 12,000 people in the United States are affected by acute spinal cord injuries similar to those found in dachshunds, and while there is a movement within the drug industry to use therapies already approved by the FDA, Levine said there are classes of FDA-approved drugs that are very similar to GM6001 that are currently being used for different treatments but, with further study, might be applicable to human spinal cord injuries as well.
“The results of this study are really encouraging in terms of a way forward,” Levine said. “There’s a lot of additional information that needs to get uncovered, but this is a first and very intriguing step at looking at how we can help people and dogs that have these injuries.”
This story by Megan Palsa originally appeared on the CVM website.